A standardized willow bark extract (STW 33-I) has been examined to clarify its possible mechanism of action as an anti-inflammatory agent. Various facets have been investigated in two inflammation models: the 6-day air pouch model in rats, representing the acute state and the adjuvant induced arthritis representing the chronic one. Parameters included leukocytic infiltration, levels of cytokines and prostanoids in blood, and effects on cyclo-oxygenase (COX)-1 and/or COX-2 enzymes as well as effects involving free radical production. The effect of the extract was compared at two dose levels with comparable anti-inflammatory doses of acetylsalicylic acid (CAS 50-78-2, ASA) as a non-selective COX inhibitor, and celecoxib (CAS 169590-42-5) as a selective COX-2 inhibitor. On a mg/kg basis, the extract was at least as effective as ASA in reducing inflammatory exudates and in inhibiting leukocytic infiltration as well as in preventing the rise in cytokines, and was more effective than ASA in suppressing leukotrienes, but equally effective in suppressing prostaglandins. On COX-2, STW 33-I was more effective than ASA. The present findings show that STW 33-I significantly raises GSH (reduced glutathione) levels, an effect which helps to limit lipid peroxidation. The extract was more potent than either ASA or celecoxib. Higher doses of the extract also reduced malondialdehyde levels and raised shows definite superiority to either ASA or celecoxib in protecting the body against oxidative stress. It is therefore evident that STW 33-I is at least as active as ASA on all the parameters of inflammatory mediators measured, when both are given on a similar mg/kg dose. Considering, however, that the extract contains only 24% salicin (molecular weight 286.2), while ASA has a molecular weight of 180.3, it follows that on a molar basis of salicin vs salicylate, the extract contains less than a sixth of the amount of salicin as the amount of salicylate in ASA. Thus it appears that STW 33-I with its lower "salicin" content than an equivalent dose of ASA, is at least as active as ASA on the measured parameters, a fact that leads one to speculate that other constituents of the extract contribute to its overall activity. The presence of polyphenols in STW 33-I probably plays a significant role in enhancing its free radical scavenging properties. The fact that STW 33-I was superior to ASA in this respect would suggest that the extract may have a better anti-inflammatory effect than ASA on a weight to weight basis, with possibly less side effects.
A specially prepared olive leaf extract (EFLA 943) has been tested for its blood pressure lowering activity in rats rendered hypertensive by daily oral doses of L-NAME (NG-nitro-L-arginine methyl ester, 50 mg/kg) for at least 4 weeks. Oral administration of the extract at different dose levels at the same time as L-NAME for a period of 8 weeks showed a dose dependent prophylactic effect against the rise in blood pressure induced by L-NAME, best effects being induced by a dose of 100 mg/kg of the extract. In rats previously rendered hypertensive by L-NAME for 6 weeks and then treated with that dose of the extract for a further 6 weeks without discontinuation of L-NAME, normalisation of the blood pressure was observed. The findings confirm previous reports on the hypotensive effects of olive leaf. The special extract, EFLA 943, was shown to give consistent results with little individual variability. The antihypertensive effect of the extract may be related to a variety of factors involving reversal of vascular changes involved in the L-NAME induced hypertension.
Extracts from the plants Iberis amara, Melissa officinalis, Matricaria recutita, Carum carvi, Mentha x piperita, Glycyrrhiza glabra, Angelica archangelica, Silybum marianum and Chelidonium majus, singly and combined in the form of a commercial preparation, STW 5 (Iberogast) and a modified formulation, STW 5-II, lacking the last 3 constituents, were tested for their potential anti-ulcerogenic activity against indometacin induced gastric ulcers of the rat as well as for their antisecretory and cytoprotective activities. All extracts produced a dose dependent anti-ulcerogenic activity associated with a reduced acid output and an increased mucin secretion, an increase in prostaglandin E2 release and a decrease in leukotrienes. The effect on pepsin content was rather variable and did not seem to bear a relationship with the anti-ulcerogenic activity. The most beneficial effects were observed with the combined formulations STW 5 and STW 5-II in a dose of 10 ml/kg b.w., comparable with cimetidine in a dose of 100 mg/kg b.w. The anti-ulcerogenic activity of the extracts was also confirmed histologically. The cytoprotective effect of the extracts could be partly due to their flavonoid content and to their free radical scavenging properties.
The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of > 15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2-5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19-52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the 'protective' cytokine IL-10. The levels of prostaglandins E2 and F2alpha and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents.
Selenium (Se) has been reported to possess anti-inflammatory properties, but its bioavailability and toxicity are considerable limiting factors. The present study aimed to investigate the possible anti-inflammatory and analgesic effects of selenium nanoparticles (Nano-Se) on inflammation induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw edema and hyperalgesia model. Leukocytic count, tumor necrosis factor-α (TNF-α), prostaglandin E (PGE), thiobarbituric acid reactive substances (TBAR), and total nitrate/nitrite (NOx) were estimated in the exudate collected from 6 day old air pouch model. Irradiated rats were exposed to 6 Gy gamma (γ)-irradiation. Nano-Se were administered orally in a dose of 2.55 mg/kg once before carrageenan injection in the first model and twice in the second model. The paw volume but not the nociceptive response produced by carrageenan in irradiated rats was higher than that induced in non-irradiated rats. Nano-Se were effective in reducing the paw volume in non-irradiated and irradiated rats but it did not alter the nociceptive threshold. The inflammation induced in irradiated rats increased all the estimated parameters in the exudate whereas; Nano-Se decreased their elevation in non-irradiated and irradiated rats. Nano-Se possess a potential anti-inflammatory activity on inflammation induced in irradiated rats.
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The present study was undertaken to investigate the pretreatment effects of standardized Ginkgo biloba extract (EGb761(®)) and low-dose whole-body γ-irradiation on the neurological dysfunction in the reserpine model of PD. Male Wistar rats were pretreated orally with EGb761 or fractionated low-dose whole-body γ-irradiation or their combination, then subjected to intraperitoneal injection of reserpine (5 mg/kg body weight) 24 h after the final dose of EGb761 or radiation. Reserpine injection resulted in the depletion of striatal dopamine (DA) level, increased catalepsy score, increased oxidative stress indicated via depletion of glutathione (GSH), increased malondialdehyde (MDA) and iron levels, decreased DA metabolites metabolizing enzymes; indicated by inhibition by glutathione-S-transferase, and nicotinamide adenine dinucleotide phosphate (NADPH)-quinone oxidoreductase (NQO) activities, mitochondrial dysfunction; indicated by declined complex I activity, and adenosine triphosphate (ATP) level and increased apoptosis; indicated by decreased mitochondrial B cell lymphoma-2 (Bcl-2) protein level and by transmission electron microscope. EGb761 and low-dose γ-radiation ameliorated the reserpine-induced state of oxidative stress, mitochondrial dysfunction, and apoptosis in brain. It can be concluded that EGb761, a widely used herbal medicine and low dose of γ-irradiation have protective effects for combating Parkinsonism possibly via replenishment of GSH levels.
These findings indicate that supplementation with either vitamin E, CoQ10 or rutin ameliorated most of the biochemical changes induced by I/R in irradiated rat brain and serum.
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